CLA-supplemented diet accelerates experimental colorectal cancer by inducing TGF-β-producing macrophages and T cells

T. G. Moreira, L. S. Horta, A. C. Gomes-Santos, R. P. Oliveira, N. M.G.P. Queiroz, D. Mangani, B. Daniel, A. T. Vieira, S. Liu, A. M. Rodrigues, D. A. Gomes, G. Gabriely, E. Ferreira, H. L. Weiner, R. M. Rezende, Laszlo Nagy, A. M.C. Faria

Research output: Contribution to journalArticle

Abstract

Conjugated linoleic acid (CLA) has been shown to activate the nuclear receptor PPAR-γ and modulate metabolic and immune functions. Despite the worldwide use of CLA dietary supplementation, strong scientific evidence for its proposed beneficial actions are missing. We found that CLA-supplemented diet reduced mucosal damage and inflammatory infiltrate in the dextran sodium sulfate (DSS)-induced colitis model. Conditional deletion of PPAR-γ in macrophages from mice supplemented with CLA diet resulted in loss of this protective effect of CLA, suggesting a PPAR-γ-dependent mechanism mediated by macrophages. However, CLA supplementation significantly worsened colorectal tumor formation induced by azoxymethane and DSS by inducing macrophage and T-cell-producing TGF-β via PPAR-γ activation. Accordingly, either macrophage-specific deletion of PPAR-γ or in vivo neutralization of latency-associated peptide (LAP, a membrane-bound TGF-β)-expressing cells abrogated the protumorigenic effect of CLA. Thus, the anti-inflammatory properties of CLA are associated with prevention of colitis but also with development of colorectal cancer.

Original languageEnglish (US)
JournalMucosal Immunology
DOIs
StateAccepted/In press - Jan 1 2018

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Conjugated Linoleic Acids
Colorectal Neoplasms
Peroxisome Proliferator-Activated Receptors
Macrophages
Diet
T-Lymphocytes
Dextran Sulfate
Colitis
Azoxymethane
Cytoplasmic and Nuclear Receptors
Dietary Supplements
Anti-Inflammatory Agents
Peptides
Membranes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Moreira, T. G., Horta, L. S., Gomes-Santos, A. C., Oliveira, R. P., Queiroz, N. M. G. P., Mangani, D., ... Faria, A. M. C. (Accepted/In press). CLA-supplemented diet accelerates experimental colorectal cancer by inducing TGF-β-producing macrophages and T cells. Mucosal Immunology. https://doi.org/10.1038/s41385-018-0090-8

CLA-supplemented diet accelerates experimental colorectal cancer by inducing TGF-β-producing macrophages and T cells. / Moreira, T. G.; Horta, L. S.; Gomes-Santos, A. C.; Oliveira, R. P.; Queiroz, N. M.G.P.; Mangani, D.; Daniel, B.; Vieira, A. T.; Liu, S.; Rodrigues, A. M.; Gomes, D. A.; Gabriely, G.; Ferreira, E.; Weiner, H. L.; Rezende, R. M.; Nagy, Laszlo; Faria, A. M.C.

In: Mucosal Immunology, 01.01.2018.

Research output: Contribution to journalArticle

Moreira, TG, Horta, LS, Gomes-Santos, AC, Oliveira, RP, Queiroz, NMGP, Mangani, D, Daniel, B, Vieira, AT, Liu, S, Rodrigues, AM, Gomes, DA, Gabriely, G, Ferreira, E, Weiner, HL, Rezende, RM, Nagy, L & Faria, AMC 2018, 'CLA-supplemented diet accelerates experimental colorectal cancer by inducing TGF-β-producing macrophages and T cells', Mucosal Immunology. https://doi.org/10.1038/s41385-018-0090-8
Moreira, T. G. ; Horta, L. S. ; Gomes-Santos, A. C. ; Oliveira, R. P. ; Queiroz, N. M.G.P. ; Mangani, D. ; Daniel, B. ; Vieira, A. T. ; Liu, S. ; Rodrigues, A. M. ; Gomes, D. A. ; Gabriely, G. ; Ferreira, E. ; Weiner, H. L. ; Rezende, R. M. ; Nagy, Laszlo ; Faria, A. M.C. / CLA-supplemented diet accelerates experimental colorectal cancer by inducing TGF-β-producing macrophages and T cells. In: Mucosal Immunology. 2018.
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abstract = "Conjugated linoleic acid (CLA) has been shown to activate the nuclear receptor PPAR-γ and modulate metabolic and immune functions. Despite the worldwide use of CLA dietary supplementation, strong scientific evidence for its proposed beneficial actions are missing. We found that CLA-supplemented diet reduced mucosal damage and inflammatory infiltrate in the dextran sodium sulfate (DSS)-induced colitis model. Conditional deletion of PPAR-γ in macrophages from mice supplemented with CLA diet resulted in loss of this protective effect of CLA, suggesting a PPAR-γ-dependent mechanism mediated by macrophages. However, CLA supplementation significantly worsened colorectal tumor formation induced by azoxymethane and DSS by inducing macrophage and T-cell-producing TGF-β via PPAR-γ activation. Accordingly, either macrophage-specific deletion of PPAR-γ or in vivo neutralization of latency-associated peptide (LAP, a membrane-bound TGF-β)-expressing cells abrogated the protumorigenic effect of CLA. Thus, the anti-inflammatory properties of CLA are associated with prevention of colitis but also with development of colorectal cancer.",
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AU - Oliveira, R. P.

AU - Queiroz, N. M.G.P.

AU - Mangani, D.

AU - Daniel, B.

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AU - Rodrigues, A. M.

AU - Gomes, D. A.

AU - Gabriely, G.

AU - Ferreira, E.

AU - Weiner, H. L.

AU - Rezende, R. M.

AU - Nagy, Laszlo

AU - Faria, A. M.C.

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